We will compare the effects of pancreozymin, secretin, and VIP analogs and peptide fragments on hormone binding to pancreatic plasma membranes and adenylate cyclase activation (in the presence of guanyl nucleotides and calmodulin). The mode of action of db-cGMP as a pancreozymin antagonist will be examined. The Ea of hormone activation of adenylate cyclase will be established by comparing native and permanently activated plasma membranes. The alpha-beta GDP analog GpSp will be used to correlate GTPase activity and the deactivation role of adenylate cyclase. The mode of action of cholera toxin on specific GTPase and on the activation process by Gpp(NH)p will be investigated. The effects of Mn2 ion, Ca2 ion, Mg2 ion, free fatty acids and a series of nucleotides and nonionic detergents on guanylate cyclases (both soluble and present in pancreatic plasma membranes) will be explored. The presence of a Ca2 ion-dependent protein kinase, the phosphorylation of plasma membrane proteins and of actomyosin will be tested in the presence of hormones. The mode of action of ethanol in vitro on pancreatic lipid metabolism will be further documented. Centro-acinar cells will be isolated by elutriation. In rat brain and natehypophysis, the specificity and number of VIP receptors, and the levels of VIP will be documented before and after weening. The concerted activation of adnylate cyclase by VIP, guanyl nucleotides and calmodulin will be studied.